1. Field of the Invention
The present invention relates to a novel method of administering aspirin, and to novel dosage forms containing same which are adapted for nasal administration.
2. Background Art
Aspirin is a well-known analgesic, antipyretic and anti-inflammatory agent widely used in the treatment of pain, fever and inflammation. It is particularly useful in the treatment of acute pain, such as post-operative pain.
Aspirin has been used in the recent past in the treatment of migraine, but with varying degrees of success. See, for example, Ross-Lee et al, Cephalalgia, Vol. 2, 9-14 (1982) and other studies referred to therein. Ross-Lee et al found that oral aspirin (900 mg) frequently relieved the pain of migraine attacks, particularly when combined with oral or intramuscular metoclopramide (10 mg). Further, those authors noted a correlation between better pain relief and higher aspirin and salicylate plasma levels. Subsequently, Noda et al, J. Neurol. Neurosurg. Psychiatry, 48 (11), 1187 (1985) reported successful treatment of migraine attacks with 497 mg of intravenous aspirin (DL-lysine-acetylsalicylate).
It is believed that aspirin can be successful in treating migraine for two reasons. When taken early in an attack, aspirin may work by inhibiting platelet aggregation, which is thought to be the biochemical trigger of migraine attacks. When administered at a later stage, aspirin or the salicylate it releases may inhibit prostaglandin synthesis and thus help to relieve pain. Nevertheless, there is evidence that early treatment is associated with better relief. See Ross-Lee et al and Noda et al, supra.
In the treatment of severe migraine, fast and reliable relief is of utmost importance. Unfortunately, it appears that aspirin is most effective and works most quickly when given intravenously. This route of administration obviously has its inherent drawbacks, including lack of patient acceptance for esthetic reasons and lack of convenience. For example, intravenous aspirin is typically administered by trained personnel in a hospital setting; it is not suitable for patient self-medication. Moreover, since aspirin is most efficacious when it is administered early in the migraine attack, immediate availability of treatment and ease of administration are especially important.
Oral ingestion would be an ideal route of administration, but absorption from oral dosage forms is slower and more erratic; moreover, vomiting often accompanies migraine, causing loss of part or all of the drug administered. Indeed, since oral aspirin is often irritating to the stomach, oral administration may even increase the tendency toward vomiting.
Rectal dosage forms of aspirin exist and might be useful in treating migraine, but would be impractical when diarrhea accompanies migraine attack. Moreover, rectal dosage forms suffer from lack of patient acceptance for esthetic reasons.
It has recently been proposed that early administration of aspirin to heart attack victims would be very beneficial in limiting damage to the cardiac muscle, due to aspirin's prevention of platelet aggregation in the arteries. During the time immediately following a heart attack, when treatment is most critical, the patient may be unconscious, making oral administration impossible. And, as in the case of migraine, oral absorption can be slow and erratic. On the other hand, intravenous administration may not be practical when it must be undertaken by paramedics in a moving ambulance. And continuation of intravenous therapy during the weeks following a heart attack is impractical, since self-medication by this route would not be feasible.
Thus, while aspirin remains the cornerstone of analgesic therapy for many types of pain, its use in the treatment of relatively severe pain, such as migraine headache and postoperative pain, and its use in the early treatment of heart attack are fraught with difficulties. Migraine and post-operative pain may respond to oral aspirin, but the response is variable and unpredictable. Intravenous administration of neutralized aspirin, on the other hand, has been found to be both effective and reliable in treating post-operative pain and in aborting migraine attacks, but this route of administration requires a skilled operator and is not suitable for patient self-medication.
Previous studies by the present inventor and coworkers have shown that selected drugs, e.g, propranolol, progesterone and estradiol, can be successfully administered nasally. See, for example, Hussain et al, J. Pharm. Sci., 68, 1196 (1979); Hussain et al, J. Pharm. Sci., 69, 1411 (1980); Hussain et al, J. Pharm. Sci., 70, 466 (1981); Hussain et al U.S. Pat. Nos. 4,284,648 and 4,315,925. Numerous other medications have thus far been administered nasally, with varying degrees of success. For an overview of the literature in this area, see "Historical Development of Transnasal Systemic Medications", Y. W. Chien and S. F. Chang, in Transnasal Systemic Medications, ed. Y. W. Chien, Elsevier Science Publishers B.V., Amsterdam, 1985, 1-99. However, the previously investigated drugs are structurally remote from aspirin, which has not been previously suggested for nasal administration.